Aging process

Aging is the process of becoming older. 

The term refers mainly to humans, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal.

Aging can refer to single cells within an organism which have ceased dividing, or to the population of a species.

Aging represents the accumulation of changes in a human being over time

Aging encompasses physical, psychological, and social changes.

Reaction time, may slow with age, while memories and general knowledge typically increase. 

Aging increases the risk of human diseases such as cancer, Alzheimer’s disease, diabetes, cardiovascular disease, stroke and many more.

Of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes.

Aging  theories are assigned to the damage concept: the accumulation of damage (such as DNA oxidation) may cause biological systems to fail, or to the programmed aging concept, whereby the internal processes (epigenetic maintenance such as DNA methylation inherently may cause aging. 

The aging process has three distinct components: physiologic degeneration, extrinsic damage (nosocusis), and intrinsic damage (sociocusis). 

These factors are superimposed on a genetic substrate, and may be overshadowed by general age-related susceptibility to diseases and disorders.

Obesity has been proposed to accelerate aging, whereas dietary calorie restriction in non-primate animals slows aging while maintaining good health and body functions. 

Human beings and members of other species, especially animals, age and die. 

Normal human cells however die after about 50 cell divisions in laboratory culture.

Teenagers lose the young child’s ability to hear high-frequency sounds above 20 kHz.

Wrinkles develop mainly due to photoageing, particularly affecting sun-exposed areas.

After peaking from the late teens to the late 20s, female fertility declines.

After age 30 the mass of human body is decreased until 70 years and then shows damping oscillations.

People over 35 years of age are at increasing risk for losing strength in the ciliary muscle of the eyes which leads to difficulty focusing on close objects, or presbyopia.

Most people experience presbyopia by age 45–50.

The cause is lens hardening by decreasing levels of alpha-crystallin, a process which may be sped up by higher temperatures.

Around age 50, hair turns grey.

Pattern hair loss by the age of 50 affects about 30–50% of males and a quarter of females.

Menopause typically occurs between 44 and 58 years of age.

In the 60–64 age cohort, the incidence of osteoarthritis rises to 53%. 

Only 20% however report disabling osteoarthritis at this age.

Almost half of people older than 75 have hearing loss inhibiting spoken communication, as they genetically lost the ability to regenerate cochlear sensory cells.

With age language can become more difficult to process resulting in a slowing of verbal comprehension, reading abilities and more likely word finding difficulties, though, functionality within daily life remains intact.

By age 80, more than half of all Americans either have a cataract or have had cataract surgery.

Frailty, a syndrome of decreased strength, physical activity, physical performance and energy, affects 25% of those over 85.

Muscles have a reduced capacity of responding to exercise or injury and loss of muscle mass and strength is common: sarcopenia 

Maximum oxygen utilization and maximum heart rate decline.

Hand strength and mobility decrease.

Atherosclerosis is classified as an aging disease, leading to cardiovascular diseases which globally is the most common cause of death.

Vessel aging causes vascular remodeling and loss of arterial elasticity and as a result causes the stiffness of the vasculature.

The maximum human lifespan is suggested to be 115 years.

Dementia becomes more common with age.

About 3% of people between the ages of 65 and 74, 19% between 75 and 84, and nearly half of those over 85 years of age have dementia.

The spectrum ranges from mild cognitive impairment to the neurodegenerative diseases of Alzheimer’s disease, cerebrovascular disease, Parkinson’s disease and Lou Gehrig’s disease. 

Many types of memory decline with aging, but not general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood.

Intelligence declines with age, though the rate varies depending on the type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. 

After 20 years of age there is a 10% reduction each decade in the total length of the brain’s myelinated axons.

Age can result in visual impairment, decreasing non-verbal communication, which can lead to isolation and possible depression. 

Older adults may not experience depression as much as younger adults, and were paradoxically found to have improved mood despite declining physical health.

Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80.

This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.

Other visual diseases that often appear with age would be cataracts and glaucoma. 

A cataract occurs when the lens of the eye becomes cloudy making vision blurry and eventually causing blindness if untreated.

Glaucoma is s  common visual disease that appears in older adults. 

Glaucoma is caused by damage to the optic nerve causing vision loss.

A distinction can be made between proximal aging- age-based effects that come about because of factors in the recent past.

Distal aging is an  age-based differences that can be traced to a cause in a person’s early life, such as childhood poliomyelitis.

Aging is among the greatest known risk factors for most human diseases.

Of the roughly 150,000 people who die each day across the globe, about two-thirds—100,000 per day—die from age-related causes.

In industrialized nations, the proportion of those who die from age-related causes, isnhigher, reaching 90%.

Factors proposed to influence biological aging fall into two main categories, programmed and damage-related.

Programmed factors of biologic aging follow a biological timetable, and 

this regulation depends on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. 

Damage-related factors in aging include internal and environmental assaults to that induce cumulative damage at various levels.

Hallmarks of aging:

genomic instability (mutations accumulated in nuclear DNA, in mtDNA, and in the nuclear lamina)

telomere attrition 

epigenetic alterations (including DNA methylation patterns, post-translational modification of histones, and chromatin remodelling)

loss of proteostasis-protein folding and proteolysis)

deregulated nutrient sensing-Growth hormone/Insulin-like growth factor 1 signalling pathway, which is the most conserved aging-controlling pathway in evolution and among its targets are the FOXO3/Sirtuin transcription factors and the mTOR complexes.

mitochondrial dysfunction 

cellular senescence-accumulation of no longer dividing cells in certain tissues

stem cell exhaustion 

altered intercellular communication-inflammation but possibly also other intercellular interactions

inflammageing-chronic inflammatory phenotype in the elderly in the absence of viral infection, due to over-activation and a decrease in the precision of the innate immune system.

Levels of TNFa, IL-6 and IL-1 can be used as inflammatory biomarkers that indicate frailty, an altered immune system, functional decline and mortality associated with inflammaging.

Dysbiosis of gut microbiome with loss of microbial diversity, expansion of enteropathogens, and altered vitamin B12 biosynthesis is correlated with biological age rather than chronological age.

There are three main metabolic pathways which can influence the rate of aging:

the FOXO3/Sirtuin pathway, probably responsive to caloric restriction, 

the Growth hormone/Insulin-like growth factor 1 signalling pathway

the activity levels of the electron transport chain in mitochondria.

DNA methylation age of blood predicts all-cause mortality in later life.

Senescent cells: most cells with DNA damages that cannot be repaired undergo apoptosis but some cells don’t. 

These cells are related to many diseases such as kidney failure and diabetes. 

It is suspected by removal of these cells life can be extended.

A variation in the gene FOXO3A has a positive effect on the life expectancy of humans, and is found much more often in people living to 100 and beyond.

Caloric restriction leads to longer lifespans in various species, probably mediated by the nutrient-sensing function of the mTOR pathway.

mTOR, a protein that inhibits autophagy, has been linked to aging through the insulin signalling pathway. 

mTOR functions through nutrient and growth cues suggesting that dietary restriction and mTOR are related in terms of longevity. 

When there is restriction in diet, mTOR activity is reduced, which allows an increased level of autophagy promoting longevity.

Autophagy recycles old or damaged cell parts, which increases longevity and decreases the chances of being obese, prevents spikes of glucose concentration in the blood, leading to reduced insulin signalling. 

Longevity is connected to caloric restriction and insulin sensitivity inhibiting mTOR, which in turns allows autophagy to occur more frequently. 

 It may be that mTOR inhibition and autophagy reduce the effects of reactive oxygen species on the body, which damage DNA and other organic material, so longevity would be increased.

Several proposed anti-aging remedies: rapamycin, metformin, berberine, 2-deoxyglucose, vitamin D3, aspirin and resveratrol suppress mTOR signaling and concurrently to reduce constitutive level of oxidative DNA damage induced by endogenous oxidants as well as to enhance the rate of autophagy.

Following nearly 1000 humans for ten years showed that while some humans do shorten their telomeres over time, a third of the participants did not.

The explains why the autosomal dominant disease, Huntington’s disease, can persist even though it is inexorably lethal. 

There are genetic variants that increase fertility in the young and increase cancer risk in the old:  genes p53 and BRCA1.

The reproductive-cell cycle theory: suggests  that aging is regulated specifically by reproductive hormones that act in an antagonistic pleiotropic manner via cell cycle signalling, promoting growth and development early in life to achieve reproduction, but becoming dysregulated later in life, driving senescence in a futile attempt to maintain reproductive ability.

The reproductive-cell cycle theory proposes that endocrine dyscrasia that follows the loss of follicles with menopause, and the loss of Leydig and Sertoli cells during andropause, drive aberrant cell cycle signalling that leads to cell death and dysfunction, tissue dysfunction/disease and ultimately death. 

Aging may  result from an increase in autoantibodies that attack the body’s tissues. 

A number of diseases associated with aging, such as atrophic gastritis and Hashimoto’s thyroiditis, are probably autoimmune.

The cellular balance between energy generation and consumption or energy homeostasis requires tight regulation during aging. 

Skin aging is caused in part by TGF-β, which reduces the subcutaneous fat that gives skin a pleasant appearance and texture. 

TGF-β blocks the conversion of dermal fibroblasts into fat cells; with fewer fat cells underneath to provide support, the skin becomes saggy and wrinkled. 

Life span, like other phenotypes, is selected for in evolution. 

Traits that benefit early survival and reproduction will be selected for even if they contribute to an earlier death. 

DNA damage theory of aging: DNA damage is thought to be the common basis of both cancer and aging.

It is thought that intrinsic causes of DNA damage are the most important drivers of aging.

Genetic damage with aberrant structural alterations of the DNA, mutational changes in the DNA sequence, and methylation of gene promoter regions or alterations of the DNA scaffolding which regulate gene expression can cause abnormal gene expression. 

DNA damage causes the cells to stop dividing or induces apoptosis, often affecting stem cell pools and hence hindering regeneration. 

Most mutations occur during embryonic and childhood development, when cells divide often, as each cell division is a chance for errors in DNA replication.

Dogs annually lose approximately 3.3% of the DNA in their heart muscle cells while humans lose approximately 0.6% of their heart muscle DNA each year: similar to the ratio of the maximum longevities of the two species (120 years vs. 20 years, a 6/1 ratio). 

Similarly,  yearly DNA loss between the dog and human occur in the brain and lymphocytes: genetic damage,, particularly gene loss is the central cause of aging.

A buildup of waste products in cells presumably interferes with metabolism, and the waste product lipofuscin is formed by a complex reaction in cells that binds fat to proteins. 

This waste accumulates in the cells as small granules, which increase in size as a person ages.

Autophagy induction enhances clearance of toxic intracellular waste associated with neurodegenerative diseases and has been demonstrated to improve lifespan in primates. 

Autophagy up-regulation can also occur during aging.

Autophagy is enhanced in obese mice by caloric restriction, exercise, and a low fat diet.

Wear-and-tear theory implies, with aging there is  damage that accumulates over time.

Accumulation of errors with aging results from chance events that gradually damages the genetic code.

Heterochromatin loss model of aging suggests transposable elements in genome disintegration as the primary role in the mechanism of aging.

It is possible aging results from accumulation of cross-linked compounds that interfere with normal cell function.

It is proposed mtDNA mutations lead to respiratory-chain-deficient cells and thence to apoptosis and cell loss. 

The Free-radical theory suggests damage by free radicals, or more generally reactive oxygen species or oxidative stress, create damage that may give rise to the symptoms of aging.

There is evidence that calorie restriction may increase formation of free radicals within the mitochondria, causing a secondary induction of increased antioxidant defense capacity.

Mitochondrial theory of aging: free radicals produced by mitochondrial activity damage cellular components, leading to aging.

The reduction of oxidative DNA damage is associated with a slower rate of aging and increased lifespan.

No lifespan data exist for humans on a calorie-restricted diet, but several reports support protection from age-related diseases.

The optimal body weight above age 65 corresponds to a leaner body mass index of 23 to 27.

The benefits of dietary restriction can also be found by changing the macro nutrient profile to reduce protein intake without any changes to calorie level, resulting in similar increases in longevity.

Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in aging.

Specifically, reducing leucine intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption.

The Mediterranean diet is credited with lowering the risk of heart disease and early death, with the major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, such as olive oil.

On the other hand, the consumption of certain foods such as sugar, refined carbohydrates, alcohol, processed meats and fried food, accelerates aging.

People who live the longest report sleeping for six to seven hours each night.

Lack of sleep (<5 hours) more than doubles the risk of death from cardiovascular disease, but too much sleep (>9 hours) is associated with a doubling of the risk of death, though not primarily from cardiovascular disease.

Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality, though the cause is probably other factors such as depression and socioeconomic status.

Sleep monitoring of hunter-gatherer tribes from Africa and from South America has shown similar sleep patterns across continents (average sleeping duration is 6.4 hours)>

There is a summer/winter difference of 1 hour.

Afternoon naps are uncommon, and insomnia is very rare, tenfold less than in industrial societies, in hunter gatherer tribes.

Physical exercise may increase life expectancy.

People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active.

Moderate levels of exercise have been correlated with preventing aging and improving quality of life by reducing inflammatory potential.

The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) minutes per week.

For example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or bicycling for 25 minutes on a daily basis would together achieve about 3000 MET minutes a week.

There is a suggestion of a relationship between regular physical exercise and cognitive functioning in old age.

Avoidance of chronic stress is associated with a slower loss of telomeres in most but not all studies, and with decreased cortisol levels. 

A chronically high cortisol level compromises the immune system, causes cardiac damage/arterosclerosis and is associated with facial aging, and the latter in turn is a marker for increased morbidity and mortality.

Loneliness carries a higher mortality risk than smoking.

Aging studies show that a healthy balance of pro and anti-inflammatory cytokine secretion is associated with successful aging whereas dysregulation of this system results in inflammaging, poor aging phenotypes, and other aging-related diseases.

Stress can be countered by social connection, spirituality, and, for men more clearly than for women, married life, all of which are associated with longevity.

Scientists have begun to explore calorie-restriction mimetics-natural and synthetic drug compounds that might yield the same health effects as calorie restriction, without dieting.

A two-year trial on nine humans using metformin to regenerate thymus tissue unexpectedly resulted in a reversal of ageing as measured by DNA methylation levels.

Cultures express age in different ways. 

The age of an adult human is commonly measured in whole years since the day of birth. 

Arbitrary divisions to mark periods of life may include: juvenile (via infancy, childhood, preadolescence, adolescence), early adulthood, middle adulthood, and late adulthood. 

Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities. 

These age specifications include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age of candidacy, and mandatory retirement age. 

Chronological aging is distinguished from social aging, cultural age-expectations of how people should act as they grow older and biological aging, an organism’s physical state as it ages.

Population aging is the increase in the number and proportion of older people in society. 

Population aging has three possible causes: migration, longer life expectancy and decreased birth rate. 

Aging has a significant impact on society: the young people tend to have fewer legal privileges, they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. 

Older people have different requirements from society and government, and frequently have differing values as well, such as for property and pension rights.

Currently, over 11% of the world’s current population are people aged 60 and older, and that by 2050 that number will rise to approximately 22%.

Aging has occurred due to better nutrition, sanitation, health care, education and economic well-being. 

Consequently, fertility rates have continued to decline and life expectancy has risen. 

Life expectancy at birth is over 80 now in 33 countries. 

Aging is occurring fastest in developing countries, including those with large youth populations.

As life expectancy rises and birth rates decline in developed countries, the median age rises accordingly: this process is taking place in nearly every country in the world.

A rising median age can have significant social and economic implications: Older people generally incur more health-related costs,  cost more in worker’s compensation and pension liabilities.

The Bureau of Labor Statistics estimated that one in four American workers were 55 or older in 2020.

The  most urgent concerns of older persons worldwide is income security. 

From a sociological  and mental health point of view aging is seen in five different views: aging as maturity, aging as decline, aging as a life-cycle event, aging as generation, and aging as survival.

Aging correlates often include economics, employment, marriage, children, education, and sense of control.

Retirement, a common transition faced by the elderly, may have both positive and negative consequences.

There is a current debate as to whether or not the pursuit of longevity and the postponement of senescence are cost-effective health care goals given finite health care resources.

Health problems become more prevalent as people get older, and include mental health problems as well as physical health problems, especially dementia.

Generally, aversion to aging is a Western attitude, while in other places around the world, old age is celebrated and honored. 

Positive self-perceptions of aging are associated with better mental and physical health and well-being.

Positive self-perception of health has been correlated with higher well-being and reduced mortality among the elderly.

This finding is generally stronger for men than women.

As people age, subjective health remains relatively stable, even though objective health worsens: This phenomenon is known as the paradox of aging.

The older people get, the more they may consider themselves in better health than their same-aged peers.

Elderly people often associate their functional and physical decline with the normal aging process.

Traditional definitions of successful aging have emphasized absence of physical and cognitive disabilities.

Successful aging involves three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement.

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